The aim of this proposal is to comparatively survey at least 100 Kb of Y specific sequence in 50 males of diverse geographic origin to discover equal to or less than 100 of evolutionary stable polymorphic markers. While the potential of the haploid, non-recombining portion of the human Y chromosome to address issues concerning the evolution of modern humans has been long recognized, progress has been slow because of an innate scarcity of variation and the inefficient means by which to identify such markers. Recently significant headway concerning the acceleration of polymorphism discovery has been achieved by systematically implementing an innovative and cost efficient method, called denaturing high-performance liquid chromatography (DHPLC). The power of the method resides in its ability to rapidly compare amplified sequences in an automated fashion, ultimately granting the opportunity to survey at least 5 million base pairs for sequence variation. DNA fragments several hundred base pairs in length will be scanned for the presence or absence of heteroduplexes, which reflect single-nucleotide base composition differences. Allele frequencies at each locus will be determined by genotyping a globally diverse collection of equal to or > 500 Y chromosomes. Population specific haplotypes will be constructed and issues relating to origins, migration patterns and degrees of male- mediated admixture will be addressed. Consequently, it should possible to reconstruct a detailed human evolutionary tree.